Aerosol generator having temperature controlled heating zone and method of use thereof

ABSTRACT

A temperature and flow rate controlled capillary aerosol generator includes two heating zones optionally separated by a region in which a pressure drop is induced. Power is metered or applied to the downstream, second zone to achieve a target resistance, and therefore a target temperature, while power is metered or applied to the upstream, first zone to achieve a target mass flow rate exiting the second zone. A target temperature is achieved in the second zone to generate an aerosol from the liquid flowing through the generator at the desired mass flow rate.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates generally to aerosol generatorsand, more particularly, to aerosol generators able to generate aerosolswithout compressed gas propellants and methods of making and using suchaerosol generators.

[0003] 2. Brief Description of the Related Art

[0004] Aerosols are useful in a wide variety of applications. Forexample, it is often desirable to treat respiratory ailments with, ordeliver drugs by means of, aerosol sprays of finely divided particles ofliquid and/or solid, e.g., powder, medicaments, etc., which are inhaledinto a patient's lungs. Aerosols are also used for purposes such asproviding desired scents to rooms, distributing insecticides anddelivering paint and lubricant.

[0005] Various techniques are known for generating aerosols. Forexample, U.S. Pat. Nos. 4,811,731 and 4,627,432 both disclose devicesfor administering medicaments to patients in which a capsule is piercedby a pin to release a medicament in powder form. A user then inhales thereleased medicament through an opening in the device. While such devicesmay be acceptable for use in delivering medicaments in powder form, theyare not suited to delivering medicaments in liquid form. The devices arealso, of course, not well-suited to delivery of medicaments to personswho might have difficulty in generating a sufficient flow of air throughthe device to properly inhale the medicaments, such as asthma sufferers.The devices are also not suited for delivery of materials inapplications other than medicament delivery.

[0006] Another well-known technique for generating an aerosol involvesthe use of a manually operated pump which draws liquid from a reservoirand forces it through a small nozzle opening to form a fine spray. Adisadvantage of such aerosol generators, at least in medicament deliveryapplications, is the difficulty of properly synchronizing inhalationwith pumping. More importantly, however, because such aerosol generatorstend to produce particles of large size, their use as inhalers iscompromised because large particles tend to not penetrate deep into thelungs.

[0007] One of the more popular techniques for generating an aerosolincluding liquid or powder particles involves the use of a compressedpropellant, often containing a chloro-fluoro-carbon (CFC) ormethylchloroform, to entrain a material, usually by the Venturiprinciple. For example, inhalers containing compressed propellants suchas compressed gas for entraining a medicament are often operated bydepressing a button to release a short charge of the compressedpropellant. The propellant entrains the medicament as the propellantflows over a reservoir of the medicament so that the propellant and themedicament can be inhaled by the user.

[0008] In propellant-based arrangements, however, a medicament may notbe properly delivered to the patient's lungs when it is necessary forthe user to time the depression of an actuator such as a button withinhalation. Moreover, aerosols generated by propellant-basedarrangements may have particles that are too large to ensure efficientand consistent deep lung penetration. Although propellant-based aerosolgenerators have wide application for uses such as antiperspirant anddeodorant sprays and spray paint, their use is often limited because ofthe well-known adverse environmental effects of CFC's andmethylchloroform, which are among the most popular propellants used inaerosol generators of this type.

[0009] In drug delivery applications, it is typically desirable toprovide an aerosol having average mass median particle diameters of lessthan 2 microns to facilitate deep lung penetration. Most known aerosolgenerators are incapable of generating aerosols having average massmedian particle diameters less than 2 microns. It is also desirable, incertain drug delivery applications, to deliver medicaments at high flowrates, e.g., above 1 milligram per second. Most known aerosol generatorssuited for drug delivery are incapable of delivering such high flowrates in the 0.2 to 2.0 micron size range.

[0010] U.S. Pat. No. 5,743,251, which is hereby incorporated byreference in its entirety, discloses an aerosol generator, along withcertain principles of operation and materials used in an aerosolgenerator, as well as a method of producing an aerosol, and an aerosol.The aerosol generator disclosed according to the '251 patent is asignificant improvement over earlier aerosol generators, such as thoseused as inhaler devices. It is desirable to produce an aerosol generatorthat is portable and easy to use.

SUMMARY OF THE INVENTION

[0011] The invention provides a capillary aerosol generator comprising aflow passage having an inlet, an outlet, a first heater in heat transfercommunication with a first zone of the flow passage adjacent the inlet,a second heater in heat transfer communication with a second zone of theflow passage adjacent the outlet, and an optional flow constriction inthe flow passage between the first zone and the second zone.

[0012] The invention also provides a process of forming an aerosol froma liquid, comprising the steps of supplying pressurized liquid to anupstream end of a flow passage of an aerosol generator including a firstheater positioned in heat transfer communication with a first zone ofthe flow passage, a second heater positioned in heat transfercommunication with a second zone of the flow passage and an optionalflow constrictor in the flow passage between the first zone and thesecond zone; measuring a parameter indicative of the mass flow rate ofthe fluid flowing through the second zone; changing the temperature inthe first zone based on the measurement of the mass flow rate of thefluid through the second zone; and heating the liquid in the second zonesuch that the liquid is volatilized and after exiting from a downstreamend of the flow passage forms an aerosol.

[0013] Still other objects, features, and attendant advantages of thepresent invention will become apparent to those skilled in the art froma reading of the following detailed description of embodimentsconstructed in accordance therewith, taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The invention of the present application will now be described inmore detail with reference to preferred embodiments of the apparatus andmethod, given only by way of example, and with reference to theaccompanying drawings, in which:

[0015]FIG. 1 schematically illustrates an inhaler incorporating amulti-zone heating apparatus in accordance with the invention;

[0016]FIG. 2 schematically illustrates an exemplary capillary aerosolgenerator (CAG) system in accordance with the present invention;

[0017]FIG. 3 schematically illustrates another embodiment of a portionof the CAG illustrated in FIG. 2;

[0018]FIG. 4 schematically illustrates another embodiment of a portionof the CAG illustrated in FIG. 2;

[0019]FIG. 5 schematically illustrates another embodiment of a portionof the CAG illustrated in FIG. 2;

[0020]FIG. 6 schematically illustrates an exemplary control scheme for aCAG in accordance with the present invention; and

[0021]FIG. 7 schematically illustrates another exemplary control schemefor a CAG in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] When referring to the drawing figures, like reference numeralsdesignate identical or corresponding elements throughout the severalfigures.

[0023] According to one aspect of the present invention, a capillaryaerosol generator incorporates two heated zones. Each zone is heated byapplying a voltage across a resistive element. The resistive elementsmay be film heaters, such as Pt heaters, applied to a supportingstructure through which the fluid flows, e.g., flow chambers such ascylindrical or rectangular flow passages incorporating the film heaters.Fluid can be supplied to the generator, preferably at a substantiallyconstant pressure, from a fluid source upstream of the generator.Alternatively, the fluid can be supplied at constant linear displacementrate by a syringe pump. The purpose of the second zone is to vaporizethe fluid as it is transported through the tube and after exiting thetube forms an aerosol. Temperature in either heating zone can bemeasured directly by thermocouples or calculated based on measurement ofa parameter such as the resistance of the heating element.

[0024] The resistive heating element of the second zone has a suitabletemperature coefficient (positive or negative) of resistance, which ispreferably a high coefficient of resistance. The second zone is heatedby the application of power to the resistive element while theresistance across the element is monitored. The monitored resistance canprovide an indication of the temperature of the heating element becausethe resistance of the heating element varies as a function of itstemperature. For example, if the resistance heater is made of platinum,the temperature coefficient of resistance of platinum is 0.00392 (°C.)⁻¹. Using the relationship R=R₀[1+α(T−T₀)], which defines theresistance value R where R₀ is the resistance at Temperature T₀ and T isthe temperature for which R is calculated, a platinum heater having aresistance of 5 ohms at 0° C., the resistance of the heater will varylinearly from about 0.55 ohms at 20° C. to about 0.9 at 200° C. Thus, bycontrolling power to a target resistance, the heater can be maintainedat a precise target temperature and thereby minimize the possibility pfthermally degrading the fluid or fluids being heated.

[0025] The resistance of the second zone's heater element can be fedback in a control scheme to meter power to the second zone, so that bymetering the power to the second zone a target resistance of the secondzone heater element is achieved, and therefore the average temperatureof the second zone's heater element can be maintained at a target value.At the same time, the power supplied to the second heater element ismeasured. This power usage data is a measure of the mass flow rate ofliquid to and through the second zone, and therefore through thegenerator as a whole. In this way, power monitoring at the second zoneserves as a mass flow meter of the fluid flowing through the generator.

[0026] According to another aspect of the invention, it is possible tocontrol an aerosol generator to deliver a target total mass (e.g., adose) of volatilized fluid. In particular, a multi-zone heatingarrangement in accordance with the invention can provide a mass flowrate through the heating arrangement which is proportional to the powerusage of the heating arrangement. Further, with such a heatingarrangement, a total mass (e.g., dose) can be made to be proportional tothe total energy used by the heating arrangement. In a medical inhaler,control of the actual dose can be obtained by controlling the fluid flowrate based on a target power level which can be achieved by timing theperiod of power supply to attain the desired total energy level.Alternatively, a target total energy level can be selected and the fluidflow rate can be adjusted to achieve that target energy level in apresent time.

[0027] As discussed briefly above, constant pressure fluid is preferablysupplied to the upstream, first zone of the generator. The rate at whichliquid is delivered from the first heating zone to the second heatingzone is dependent upon the pressure drop across the entire fluid channeldownstream of the pressure source. According to yet another aspect ofthe present invention, a segment of small bore tubing, a porous pressuredrop element, or other element which functions to throttle fluid flow,is positioned between the outlet of the first zone and the inlet of thesecond zone. The pressure drop across this element is designed to be alarge fraction of the pressure drop across the entire fluid channeldownstream of the pressure source and is a function of or depends uponthe viscosity of the liquid, which in turn depends upon the temperatureof the fluid. The application of power to the first zone is controlledto control this temperature and thus the liquid flow rate through thefirst zone. Power applied to the first zone is controlled to achieve atarget power usage in the downstream, second zone, required to maintainthe second zone's heater element at a target temperature. In thismanner, power control in the first zone serves as a mass flow controllerof fluid flowing through both of the first and second zones andtherefore the generator as a whole.

[0028] The feedback control scheme implemented is designed so that atarget flow rate through the generator is achieved when the temperatureof the liquid exiting the first zone is at a target temperature abovethe highest anticipated ambient temperature in which the generator wouldbe used. In this way, the mass flow rate can be controlled to its targetvalue independent of ambient temperature and independent of the pressureapplied to the liquid, because the temperature of the liquid enteringthe second zone is substantially the same across a wide range of ambientenvironmental temperatures and because the source of fluid supplies thefluid at a substantially constant pressure. A generator according to thepresent invention therefore is capable of reducing the likelihood ofoverheating the liquid, and controlling the aerosol delivery rate in thepresence of variations in ambient temperature and pressure applied tothe liquid.

[0029] One object of the present invention is to provide controlledheating along the length of the capillary tube used to heat and vaporizea flowing liquid inside the tube. There are numerous benefits which canbe achieved through the use of this approach to heating. As overheatingthe fluid is not desirable and if sections of the tube walls become toohot due to localized vaporization or bubbles in the liquid stream, theliquid materials may be thermally degraded. The present inventioninstead provides multiple heated areas which can be easily monitored andreadily react to a control scheme. Furthermore, a generator according tothe present invention is thus capable of compensating for materialswhich are not delivered to the tube at optimum temperatures. Further, agenerator according to the present invention is capable of reacting toor accommodating changes in flow rates and liquid density inside thetube after the fluid has been introduced into the generator, and theseveral heating segments can actively respond to the output of sensorsindependent of the other segments.

[0030] According to a first exemplary embodiment, a capillary aerosolgenerator comprises a capillary tube having a inlet port, an outletport, and a lumen extending through the tube from the inlet port to theoutlet port, a first heater in heat transfer communication with a firstzone of the tube adjacent to the inlet port, a second heater in heattransfer communication with a second zone of the tube adjacent to theoutlet port, a flow constriction in the tube lumen between the firstzone and the second zone.

[0031] According to a second exemplary embodiment, a process of formingan aerosol from a liquid comprises the steps of providing an aerosolgenerator including a tube, a first heater positioned in heat transfercommunication with a first, upstream zone of the tube, a second heaterpositioned in heat transfer communication with a second, downstream zoneof the tube, and a flow constrictor in the tube between the first zoneand the second zone, supplying the liquid at a pressure to an upstreamend of the tube, measuring a characteristic of the tube indicative ofthe mass flow rate of the fluid flowing through the tube in the secondzone, changing the temperature of the tube in the first zone based onthe measurement of the mass flow rate of the fluid through the secondzone, and allowing the liquid to exit the tube at a downstream end ofthe tube.

[0032] In developing capillary aerosol generators it is desirable toimprove control of the rate at which liquid is introduced into thecapillary tube and the rate at which power is metered to the capillarytube's heater. Failure to correctly control these parameters can resultin overheating of the liquid, resulting in thermal degradation of theliquid material and subsequent clogging of the capillary by thebyproducts of this thermal degradation.

[0033] One aspect of the present invention is the reduction in thelikelihood that the liquid in the capillary tube is improperly heated,by controlling the energy supplied to a liquid vaporization zone (adownstream, second heating zone) to achieve a target temperature, whilecontrolling the energy supplied or power metered to a liquid flow ratecontrol zone (an upstream, first zone) to achieve the target liquid flowrate emerging from the aerosol generator. The capillary aerosolgenerator according to the present invention includes heating elementsand associated control circuitry which function as heating elements aswell as flow meters and flow controllers.

[0034] According to a preferred embodiment, the present inventionprovides a capillary aerosol generator which includes a system forheating an essentially hollow, tubular structure using a series ofheated zones to allow for different temperatures and rates of heatingalong the length of the tubular structure. The system includes a seriesof discrete heating elements along the length of the structure, oralternative arrangement such as by segmenting a continuous resistiveheater using independent contacts along the length of the resistor. Theresistive array of single resistive elements can have purposeful spacingbetween the heated sections and incorporate current, voltage, and/ortemperature sensing devices along the tube length that can passivelysense or be part of an active control system. The control systemactivates the individual heaters with a sequence of currents, voltages,or both, which delivers electrical power to the tube. Additionally, thecontrol system can interact with and react to one or more of thesensors. Alternatively, the heaters can be inductive heaters instead ofresistive heaters. The heater materials can be an integral part of thetube's walls or independent elements added to the structure.

[0035]FIG. 1 shows an inhaler 500 incorporating a multi-zone heater 510in accordance with the invention. The inhaler 500 includes a firsthousing 520 having a mouthpiece 522 and second housing 530 whichincludes power source and logic circuitry as discussed in copendingapplication Ser. No. 09/172,023, filed Oct. 14, 1998, the disclosure ofwhich is hereby incorporated by reference. An aerosol is generated by aheated tube 540 incorporating the multi-zone heater 510. Liquid from apressurized source 550 passes through a valve 560 and into a firstheated zone Z1 of the tube 540 and the vapor is generated in a secondzone Z2 of the tube 540. The vapor mixes with air inside the housing 520to form an aerosol and the resulting mixture can be inhaled through themouthpiece 522.

[0036]FIG. 2 schematically illustrates an exemplary capillary aerosolgenerator (CAG) system 600 in accordance with the present invention. CAGsystem 600 includes a source of pressurized fluid 604, a CAG 602, and avalve 606. Valve 606 controls the flow of pressurized fluid from source604 to CAG 602, and can be controlled either manually or, morepreferably, under control of a controller, as described in greaterdetail below. A controller 608 is also provided for controlling theoperation of CAG 602, and optionally also controls valve 606. Valve 606can alternatively be controlled by a separate controller (notillustrated).

[0037] CAG 602 is divided into at least two heating zones: an upstream,first zone Z1; and a downstream, second zone Z2. The two zones can beoptionally separated by an intermediate zone Z3. Each of zones Z1, Z2includes an electrical heating element which heats up upon theapplication of a voltage across and current through the heating element,as will be readily appreciated by one of ordinary skill in the art.Controller 608 is placed in electrical communication with and acrossboth zones Z1 and Z2, as illustrated in FIG. 2, and selectively appliesvoltage across and current through the heaters in the zones. Controller608 can be provided with a memory 610 in which an instruction set foroperation of the controller can be stored. Controller 608 can be ageneral purpose digital computer which operates under software control,the set of software instructions being stored in volatile ornon-volatile memory 610, or optionally and alternatively controller 608can be a specially constructed, expert controller including discretedigital or analog components which together embody the instruction setfor controller 608. As the specific construction of controller 608 willbe readily appreciated by one of ordinary skill in the art upon acomplete reading of the descriptions herein, no further description ofthe specific design of controller 608 will be undertaken.

[0038]FIG. 3 illustrates another embodiment of a CAG in accordance withthe present invention, CAG 612. CAG 612 includes a first, upstream tube614 and a second, downstream tube 616. First tube 614 includes aproximal inlet 618, a flow passage 620, and a distal outlet 622. Inlet618 is in fluid communication with source 604, as described above, anddirects a fluid, preferably a liquid, along a fluid flowpath 624downstream to outlet 622. Second tube 616 is positioned downstream ofoutlet 622, and includes a proximal inlet 626, a flow passage 628, and adistal outlet 630. As illustrated in FIG. 2, first tube 614 has a fluidflow cross section which is greater than the fluid flow cross section ofsecond tube 616, and inlet 626 is positioned at outlet 622, i.e., thereare no structures between inlet 626 and outlet 622.

[0039] First tube 614 and second tube 616 include a heater element orelements therein or thereon to which controller 608 is electricallyconnected. The heaters can be made integral with the tubes, such as byforming the tubes themselves of a material which is sufficientlyelectrically resistive to act as an electrical heater for the fluidcontents of the tube. Alternatively, tubes 614, 616 can include one ormore internal or external heaters mounted to the tubes which heat when avoltage is applied to them, and which in turn heat the tubes and theirfluid contents. Controller 608, in accordance with the instruction setcontained in memory 610 or the logic of its discrete elements,selectively applies a voltage to the heater associated with one or bothof tubes 614, 616. The voltage applied causes the heater element(s) toincrease in temperature, which in turn heats the fluid contents of therespective tube by convection and/or conduction. As described in greaterdetail herein, one or both of tubes 614, 616 and their fluid contentscan be selectively heated. At the same time, a parameter such asresistance of the heater element heating the tube 614 can be measured tomonitor the temperature of the tube 616 and the power used to heat thetube 616 can be measured to determine the mass flow rate of fluidflowing through the CAG.

[0040] As outlet 630 is the port from which vaporized fluid exits CAG612, it is preferable that outlet 630 is unobstructed so that the flowof fluid out of CAG 612 is not impeded at outlet 630. Furthermore, byproviding a zone of reduced cross section downstream of the first tube614, a throttle is formed which induces a pressure drop. This optionalthrottle or other constriction which causes a drop in fluid pressure inCAG 612 is located downstream of first tube 614 and is substantiallyconfined to zone Z3 (see FIG. 2). By forming a structure in CAG 612which induces or causes a drop in fluid pressure in the flow passages oftubes 614, 616, it is possible to control the mass flow rate of fluidflowing through the CAG. It is therefore preferable that tubes 614, 616include no or substantially no source of a reduction in fluid pressurealong their lengths, so that the mass flow rate of fluid through the CAGcan be determined and maintained at a desired level by controller 608.

[0041]FIG. 2 illustrates that controller 608 is electrically connectedto first tube 614 to define first zone Z1, and electrically connected tosecond tube 616 to define second zone Z2. CAG 612, as with otherembodiments of CAG 602 described herein, may optionally include atemperature sensing device 632 attached to or formed in the distal endof second tube 616. Temperature sensor 632 can be a thermistor or othertemperature sensitive device which can provide a signal which includesdata representative of the temperature of the distal end of second tube616. Temperature sensor 632 can be in electrical communication withcontroller 608 so as to provide a signal indicative of the temperatureof the distal end of second tube 616 to the controller to provide afeedback signal for controlling the application of power to first tube614, second tube 616, or both, as described in greater detail below.

[0042] Turning now to FIG. 3, yet another embodiment of CAG 602, CAG640, is illustrated. CAG 640 is similar in many respects to CAG 612,except that CAG 640 is formed as a monolithic, integral, unitarystructure formed as a single piece. A first, proximal, upstream portion642 receives pressurized fluid from source 604, as described above. Anoptional flow constrictor 644 is formed distally downstream of portion642, and creates a drop in fluid pressure. A second, distal portion 646is formed downstream of constrictor 644, and includes a distal exit port648 from which vaporized fluid exits CAG 640. Thus, zone Z1 includesportion 642, zone Z2 includes portion 646, and zone Z3 includesconstrictor 644. As in CAG 612, the heater elements for each of portions642, 646 can be a portion of the walls of the CAG, attached to the wallsof the CAG, or combinations thereof.

[0043]FIG. 4 schematically illustrates yet another embodiment, CAG 660.Similar to CAG 640, CAG 660 is preferably formed from a single piece ofmaterial and is electrically connected to controller 608 to define zonesZ1, Z2, and Z3, as described above. Different from CAGs 612, 640, CAG660 has a constant internal flow cross-sectional area in zones Z1 andZ2, and an optional constrictor 662 is mounted or otherwise provided inzone Z3 to cause a drop in fluid pressure. Preferably, constrictor 662is a porous plug formed of a material non-reactive to the fluid intendedto flow through CAG 660, and includes pores therein which allow thefluid to flow through the plug and the CAG. Constrictor 660 is designedto provide a drop in fluid pressure between zones Z1 and Z2 at apredetermined fluid pressure and viscosity, in a manner well appreciatedby one of ordinary skill in the art.

[0044] The function of controller 608 with CAG 612, 640, or 660 will nowbe described with reference to FIG. 5. Throughout this description,several variables will be discussed, as follows:

[0045] V(Z1) . . . voltage across zone Z1

[0046] V(Z2) . . . voltage across zone Z2

[0047] P(Z1) . . . electrical power used in zone Z1

[0048] P(Z2) . . . electrical power used in zone Z2

[0049] T(Z1) . . . average temperature of CAG in zone Z1

[0050] T(Z2) . . . average temperature of CAG in zone Z2

[0051] T(Z3) . . . average temperature of CAG in zone Z3

[0052] T(Z2′) . . . temperature of CAG at distal end of zone Z2

[0053] r(Z1) . . . electrical resistance of portion of CAG in zone Z1

[0054] r(Z2) . . . electrical resistance of portion of CAG in zone Z2

[0055] M . . . mass flow rate of fluid

[0056] M(Z) . . . mass flow rate of fluid flowing through zone Z1

[0057] M(Z2) . . . mass flow rate of fluid flowing through zone Z2

[0058] pr(Z1) . . . fluid pressure drop across zone Z1

[0059] pr(Z2) . . . fluid pressure drop across zone Z2

[0060] pr(Z3) . . . fluid pressure drop across zone Z3

[0061] η . . . fluid viscosity

[0062] From the foregoing description, because there is no loss of fluidin the CAG between zones Z1 and Z2, the mass flow rates through thesezones are identical, or

M(Z1)=M(Z2)=M

[0063] As well appreciated by one of ordinary skill in the art, theelectrical power (P) of an electrical component, its resistivity (r),the current (i) flowing through the element, and the electricalpotential or voltage (V) across the element are interrelated, accordingto well-known relationships:

V=ir

p=i²r

P=iV

P=V ² /r

[0064] Additionally, because of the design of the CAGs of the presentinvention, several other relationships can be used to measure andcontrol electrical and physical characteristics of the CAG and the fluidflowing therethrough. It has been found by the inventors herein that thepower consumed by the portion of the CAG in zone Z2 to maintain thatportion of the CAG at a known temperature (the boiling point for theliquid being aerosolized, for example) is a function of the mass flowrate through the CAG:

P(Z2)=F(M)

[0065] The exact functional relationship between power and mass flowrate can be readily empirically determined, as will be readily apparentto one of ordinary skill in the art. Once this functional relationshipis determined, it is used to form the instruction set in memory 610, orto design the logic of controller 608, as described below.

[0066] The materials from which the CAGs are formed, along with theheater elements themselves, are selected so that the averagetemperatures of zones Z1 and Z2 are functions of the resistance of theportions of the CAGs which are in these zones:

T(Z1)=F(r(Z1))

[0067] and

T(Z2)=F(r(Z2))

[0068] Many materials, e.g., copper, stainless steel, and platinum,exhibit this relationship between temperature and resistance, and thefunction is linear over a wide range of temperatures. Thus, the materialout of which the CAGs are formed, or at least the heater elements, ispreferably selected to have a temperature-resistance function which iswell known, and preferably linear, over the range of temperatures inwhich system 600 will be used and the fluid will be aerosolized at leastin the case where the resistance of the heater element is used tomeasure the temperature of the tube.

[0069] The CAG is preferably designed so that when controller 608attempts to maintain the power consumed by the portion of the CAG inzone Z2 at its target level, P (target), the temperature of zone Z1 willbe at a level, which is preferably at or slightly above the highestambient temperature at which it is anticipated that system 600 would beused.

[0070] Additionally, the fluid to be aerosolized is preferably deliveredto zone Z1 by applying a constant pressure P. The fluid pressure dropsacross zones Z1 and Z2 are preferably close to zero:

pr(Z1)≈pr(Z2)˜0

[0071] in which case:

P≈pr(Z3)

[0072] Furthermore, the pressure drop across zone Z3 is related to themass flow rate of the fluid flowing through the CAG and the viscosity,eta, of the fluid in zone Z3, according to the relationship:

pr(Z3)=k*M/eta

[0073] where k is a constant dependent upon the geometry of the channelin zone (Z3) and eta is the viscosity of the fluid in this zone, whichviscosity is a function of the temperature of the fluid, that is:

eta=F(T(Z3))

[0074] Therefore:

P˜k*M/eta

[0075] or

M˜P*eta/k

[0076] Thus, the mass flow rate of fluid through the CAG is determinedby the applied pressure and the viscosity of the fluid in zone Z3. Thislatter quantity is, in turn, controlled by the temperature in zone Z3.It is for this reason that the flow constrictor is preferably provided,i.e., so that the mass flow rate can be more accurately controlled byadjusting the temperature in zone Z3.

[0077] These several functional interrelationships having beenestablished, an exemplary control scheme for controller 608 will now bedescribed with reference to FIG. 5. At the initiation of a cycle ofgenerating a predetermined amount or bolus of aerosolized liquid, valve606 is opened, allowing liquid at a known and preferably constantpressure to enter the CAG. At step 700, controller 608 applies andcontrols voltages across Z1 and Z2 to raise the temperature of the fluidtherein. At step 702, the controller measures resistance r(Z2), tomeasure T(Z2). Alternatively, or as a redundant measurement, thecontroller measures T(Z2′) at step 704 at the exit of zone Z2 with thethermocouple or thermistor. At step 706, the controller then comparesthe measured value of T(Z2), and adjusts V(Z2), and therefore P(Z2), toachieve a measured, target r(Z2), and therefore a target T(Z2). As willbe readily appreciated by one of ordinary skill in the art, thetemperature achieved can be within a predetermined range and stillsatisfy this condition, i.e., a certain, predetermined error isacceptable.

[0078] The controller then measures P(Z2) at step 708 which was neededto maintain T(Z2) at (or acceptably near) the target value, which givesa measure of the mass flow rate M of fluid flowing through the CAG, asdiscussed above. At step 710, the controller evaluates if the powermeasured to maintain the proper temperature, P(Z2), is greater than thepower necessary, P(target), from the empirical relationship betweenpower and mass flow rate. If so, the controller decreases the voltage,and therefore the power, applied to zone Z1. This is because when themass flow rate is higher than desired, the fluid flowing through the CAGwill cool the zone Z2, requiring additional power to heat zone Z2 to thetarget temperature. A decrease in the voltage applied across zone Z1lowers the temperature of the fluid therein, and therefore raises theviscosity, and therefore lowers the mass flow rate through zone Z2. Thishas the effect of making zone Z1 a flow controller for the CAG, andmaking zone Z2 a flow monitor for the CAG. Similarly, at step 712 if thepower measured across zone Z2 to achieve the target temperature T(Z2) isless than the target power, the controller increases the voltage across(and therefore the power used by) zone Z1 to increase the temperature ofthe fluid flowing through zone Z1, and thereby raises the mass flowrate.

[0079] At step 714, the controller sums or integrates mass flow rateover time to determine the total mass (m) delivered during the cycle. Atstep 716, the total mass m delivered is compared with a predetermineddesired value of m. If the total mass actually delivered is less thanthe amount desired to be delivered, then the controller returns to step700. If the total mass delivered is equal to or greater than the totalmass desired, the flow of fluid from the source 604 is terminated byvalve 606, and the voltage(s) across zones Z1 and Z2 are set to zero.

[0080]FIG. 6 schematically illustrates a control scheme for controller608 which assists in determining if a fault condition exists in the CAG.The control scheme illustrated in FIG. 6 can be integrated into thecontrol scheme illustrated in FIG. 5 and described with referencethereto, or can precede or follow the control scheme of FIG. 5. In step730, the power consumed in zone Z2 is measured, which is a measure ofthe mass flow rate through zone Z2. The temperature of zone Z2 is thenmeasured in step 732, either by measuring the resistance of the heaterelement in zone Z2, or by measuring the temperature T(Z2′) at thethermocouple as at step 734.

[0081] At step 736, the controller determines whether the powerconsumption measured at zone Z2 is less than P(target), and thecontroller increases the voltage across (and therefore the powerconsumed by) zone Z1, to increase the mass flow rate M. However, thisaction may fail to increase P(Z2) to P(target). A power consumptionmeasurement which is low for the temperature measured can be indicativeof a blockage in the flow passage of the CAG, which would lower the massflow rate and the power P(Z2) required to achieve the target T(Z2). Inthis event, an alarm could be sounded, and the apparatus shut down.

[0082] At step 738, the controller determines whether the powerconsumption measured at zone Z2 is greater than P(target), and thecontroller decreases the voltage across (and therefore the powerconsumed by) zone Z1, to decrease the mass flow rate M. However, thisaction may fail to decrease P(Z2) to P(target). A power consumptionmeasurement which is high for the temperature measured can be indicativeof an overflow condition in the flow passages of the CAG, which wouldraise the mass flow rate and the power P(Z2) required to achieve thetarget T(Z2). In this event, an alarm could be sounded, and theapparatus shut down.

[0083] According to the invention, a control algorithm can be used tomaintain a downstream heater at a desired target resistance. Once steadystate operation is achieved (e.g., in less than 100 msec), the algorithmcan calculate the energy consumption (power) in the downstream heaterbased on an arbitrary time scan (e.g., 32 msec average). The frequencyat which the upstream heater is pulsed can be adjusted up or down as afunction of whether the downstream heater is operating at a desiredtarget power. If the power in the downstream heater is below the targetlevel, the time between the upstream heater pulses can be decreased tothereby increase the temperature in the upstream heater zone.

[0084] Experiments in which energy consumption and mass delivery arecompared as a function of feed pressure are shown in FIGS. 8 and 9wherein FIG. 8 shows power as a function of feed pressure of propyleneglycol in the case where the upstream heater is turned off, the run timeis 10 seconds and the downstream resistance target is 0.36 ohms. FIG. 9shows aerosol mass delivery under the same conditions as used in FIG. 8.Thus, FIGS. 8 and 9 show typical one heating zone response to increasingfeed pressure. As shown, the power usage and aerosol mass increase in alinear fashion with increasing pressure.

[0085] In two-zone experiments, the downstream heater target power levelwas 2.6 watts, the upstream heater was turned off, and the feed pressurewas 20 psi. The initial setting for the upstream heater was to supplypower to the upstream heater once every 8 msec. Further, pressure wasvaried from 6 to 30 psi and the energy usage and mass deliveries weremeasured. FIG. 10 shows power curves as a function of pressure for thedownstream heater, the upstream heater and both heaters, the downstreamheater target resistance being set at 0.36 ohms, the downstream heatertarget power being set at 2.6 watts and the fluid being propyleneglycol.

[0086]FIG. 11 shows the aerosol mass delivery for propylene glycol (PG)in a two-zone heater wherein the run time was 10 seconds, the downstreamheater target resistance was 0.36 ohms, the upstream heater firingfrequency was once every 8 msec and the downstream heater target powerwas 2.6 watts. Results for one-zone heating was added to FIG. 11 forcomparison. As shown, the aerosol mass delivery for the two-zone heatingarrangement remains relatively constant over the feed pressure range of6 to 20 psi. Above 20 psi, the aerosol mass delivery tracks the one-zonedata because the target power level was set for the 20 psi case and theupstream heater is unable to cool the PG to compensate for an increasein pressure above this target. Accordingly, heating the PG to reduce itsviscosity and increase its flow rate can be used to compensate forpressure variations and/or temperature variations. Moreover, theseexperiments demonstrate that power consumption of the downstream heatercan be used as a feedback signal to control the upstream heater power.In the case illustrated in FIG. 11, a 32 msec power average was used forthe downstream heater and the heating arrangement responded rapidly toachieve the desired targets.

[0087] While the invention has been described in detail with referenceto preferred embodiments thereof, it will be apparent to one skilled inthe art that various changes can be made, and equivalents employed,without departing from the scope of the invention.

What is claimed is:
 1. An aerosol generator comprising: a flow passagehaving an inlet and an outlet; a first heater in heat transfercommunication with a first zone of the flow passage; and a second heaterin heat transfer communication with a second zone of the flow passage,the second heater being downstream of the first heater.
 2. A capillaryaerosol generator according to claim 1, further comprising a flowconstriction in the flow passage between the first zone and the secondzone.
 3. A capillary aerosol generator according to claim 1, furthercomprising a controller in electrical communication with the firstheater and the second heater, the controller selectively supplying avoltage across the first heater and the second heater.
 4. A capillaryaerosol generator according to claim 3, wherein the controllerselectively measures the resistance of the heater in the first zoneand/or the second zone.
 5. A capillary aerosol generator according toclaim 3, wherein the controller selectively measures the voltage acrossthe first zone and the second zone.
 6. A capillary aerosol generatoraccording to claim 3, wherein the controller comprises a memoryincluding an instruction set which instructs the controller when tomeasure resistance, when to measure voltage, and when to apply voltageto the first zone, the second zone, or both.
 7. A capillary aerosolgenerator according to claim 1, wherein the flow passage comprises afirst tube including the inlet wherein the first heater is in heattransfer communication with the first tube and a second tube includingthe outlet wherein the second heater is in heat transfer communicationwith the second tube.
 8. A capillary aerosol generator according toclaim 7, wherein the flow passage in the first tube has a first innerdiameter and the flow passage in the second tube has a second innerdiameter, the first inner diameter being greater than the second innerdiameter.
 9. A capillary aerosol generator according to claim 7, whereinthe second tube is partially mounted in the first tube.
 10. A capillaryaerosol generator according to claim 2, wherein the flow passage is in amonolithic, single-piece element, and the flow constrictor is integrallyformed in the flow passage.
 11. A capillary aerosol generator accordingto claim 2, wherein the flow constrictor comprises a porous plugpositioned in the flow passage.
 12. A capillary aerosol generatoraccording to claim 1, further comprising a temperature sensor in heattransfer communication with the flow passage in the second zone.
 13. Asystem useful for generating an aerosol, comprising: a capillary aerosolgenerator according to claim 1; a source of pressurized fluid; and avalve between the source of pressurized fluid and the capillary aerosolgenerator.
 14. A system according to claim 13, wherein the valve is anautomatically controllable valve, and further comprising a controller inelectrical communication with the first heater, the second heater, andthe valve, the controller selectively supplying a voltage across thefirst heater and the second heater, and the controller operative toselectively open and close the valve.
 15. A process of forming anaerosol from a liquid, comprising the steps of: supplying pressurizedliquid to an upstream end of a flow passage of an aerosol generatorincluding a first heater positioned in heat transfer communication witha first zone of the flow passage and a second heater positioned in heattransfer communication with a second zone of the flow passage, thesecond zone being downstream of the first zone; measuring a parameterindicative of the mass flow rate of the fluid flowing through the flowpassage in the second zone; changing the temperature in the first zonebased on the measurement of the mass flow rate of the fluid through thesecond zone; and heating the liquid in the second zone such that theliquid is volatilized and sprayed from a downstream end of the flowpassage in the form of an aerosol.
 16. A process forming an aerosolaccording to claim 15, wherein the liquid passes through a flowconstrictor in the flow passage between the first zone and the secondzone.
 17. A process of forming an aerosol according to claim 15, furthercomprising the steps of: measuring the temperature in the second zone;and adjusting a voltage across the second heater based on thetemperature measured in the second zone.
 18. A process of forming anaerosol according to claim 15, wherein the step of changing thetemperature in the first zone comprises the steps of: comparing thepower consumed in maintaining the temperature of the second heater at apredetermined temperature (P(Z2)) to a target power level (P(Target));decreasing the power applied to the first heater if (P(Z2))>(P(Target));and increasing the power applied to the first heater if(P(Z2))<(P(Target)).